In order to suppress or reduce immune responses in inflammatory diseases, immunomodulatory drugs often need to be administered systemically, so that they can reach the lymphoid organs at the effective concentrations that are required to modulate the immune response. This results in systemic spread of the immunomodulatory drug throughout the body, causing unwanted off-target side effects. Moreover, most of these drugs have to be administered by intravenous injection, which is burdensome for patients and carry additional risks such as infusion reactions and infections. Administration of immunomodulatory drugs through the skin or by inhalation has been restricted to treatment of localized autoimmune or hypersensitivity reactions that affect the skin or the airways (e.g., psoriasis or asthma, respectively.
Epidemiological studies have associated vitamin D deficiency with a variety of diseases including type I diabetes (T1D). The impact of vitamin D deficiency on immune cells has been thought to be direct, with studies showing that vitamin D can directly suppress the activation of immune cells such as T cells, dendritic cells, monocytes/macrophages, and B cells. However, clinical trials to investigate the effects of oral or intravenous vitamin D supplementation in patients have been met with limited success. The effects of vitamin D supplementation was ineffective or modest at best, because the doses of vitamin D that need to be administered systemically for therapeutic effect cause serious side effects such as hypercalcemia.
There is thus a need in the art to develop novel methods of suppressing systemic immune responses in a subject. Such methods should be useful in treating systemic inflammatory diseases and avoid serious side effects associated with the drug's systemic exposure. The present invention fulfills this need.